Use of water-soluble, high-molecular substances as the carriers for drugs, namely, pharmaceutical compounds has been attempted to date especially in the field of pharmaceutical preparations, and a number of related techniques have been provided. These water-soluble, high-molecular substances as the drug carriers are already known widely. In many instances, a cellulose derivative such as carboxymethylcellulose, hydroxypropylcellulose or hydroxypropylmethylcellulose is used. However, these conventional techniques are concerned with so-called sustained release of drugs and have not been developed to techniques for delivery of a drug to a tissue where the drug is required, when necessary, only in an amount as needed. It is the current situation that no satisfactory technique has been developed yet for using a water-soluble, high-molecular substance as a carrier for delivery of the drug. For example, there are the below-described publications 1) and 2). The publication 1) discloses use of carboxymethylchitin as a fine particulate carrier of the implanted type, whereas the publication 2) discloses use of carboxylated dextran as a carrier for the formation of its complex with a drug.
1) WATANABE, K. et al., "Chem. Pharm. Bull.," 38, 506-509, (1990), and PA1 2) SEZAKI, Hitoshi, "Yakugaku Zasshi,: 109, 611-621, (1989) PA1 P-Phe-Phe-Gly-, PA1 P-Gly-Phe-Gly-Gly-, PA1 P-Phe-Gly-Phe-Gly-, PA1 P-Gly-Phe-Gly-Phe-, PA1 P-Gly-Gly-Gly-, and PA1 P-Ala-Gly-Gly-Gly-. PA1 -Suc-Ala-Ala-Ala-P, and PA1 - Suc-Ala-Ala-Val-Ala-P PA1 (i) H-Gly-Gly-Gly-Val-Ala-OH, -Gly-Gly-Gly-Leu-Ala-, -Gly-Gly-Phe-Leu-Gly-, -Gly-Gly-Phe-Try-Ala-, -Gly-Gly-Gly-Gly-Gly-, PA1 (ii) -Gly-Gly-Gly-Phe-Leu-Gly-, -Gly-Gly-Gly-Gly-Leu-Ala-, -Gly-Gly-Gly-Gly-Gly-Gly, PA1 (iii) -Gly-Gly-Gly-Gly-Phe-Leu-Gly-, -(Gly).sub.7 -, -(Gly).sub.5 -Lue-Ala-, PA1 (iv) --(Gly).sub.5 -Phe-Leu-Gly, -(Gly).sub.8 -, PA1 (v) -(Gly).sub.9 -, and PA1 (vi) -(Gly).sub.10 -. PA1 3) OKIMASU, Satoru, "Journal of the Society of Agricultural Chemistry", 32, 303-308, (1958)
Although the technique disclosed in the publication 1) perceived the gelling ability and the in vivo biodegradability of carboxymethylchitin and makes use of these properties, carboxymethylchitin is of the type which is implanted to a particular local site in the body so that this technique does not go beyond the boundary of the controlled release of a drug and is not expected to enhance the organotropism of a drug to a target cancer tissue or a target organ. On the other hand, the drug complexes disclosed in the publication 2) suggests the possibility of excellent drug-delivery, but functional groups of said carboxylated dextran which are usable for the molecular modification of drug-complexes to facilitate the delivery of drugs are limited to alcoholic hydroxyl groups.
Reflecting the development of an increasing number of the anticancer agents, brain disease-curing drugs and the like, there is an outstanding need for the urgent establishment of targeting technology for these drugs with using a water-soluble, high-molecular substance. Nevertheless, the prior art techniques have not brought about any fully satisfactory solution.
To complete a targeting technique for drugs, namely, pharmaceutical compounds, by using a water-soluble, high-molecular carrier, it is necessary as prerequisites therefor, firstly that a complex of carrier with a drug remains stable in blood after its administration by intravenous injection until its arrival at a target organ, in other words, the drug can be maintained at a necessary concentration in blood, secondly that the carrier is subjected to gradual degradation in the body and consequently the carrier does not remain for a long time in the human body, and thirdly that the carrier as linked to the drug in the form of the complex exhibits by itself the tendency of an organotropism in vivo. Therefore a carrier must be provided, first of all, as one being capable of meeting these requirements all together.